FM-fMRI: Event Conditioned Flow Matching for Rest-to-Task fMRI Time-Series Synthesis

Flow matching and diffusion models enable conditional generation across domains ranging from images to proteins, with recent extensions to out-of-distribution contexts. Yet generative models of neural time series have largely remained restricted to categorical conditioning, precluding compositional and zero-shot generalization. In this work, we propose a per-timestep conditioned diffusion transformer for generating realistic fMRI brain dynamics during unseen cognitive tasks by injecting both compositional language and optional spatial priors in-context. Such zero-shot generation could enable counterfactual neuroscience by supporting in-silico design and evaluation of novel cognitive experiments before empirical validation. Leveraging this model, we evaluate across hundreds of held-out task conditions and characterize predictive performance in relation to the training manifold. From language alone, the model recovers region-specific recruitment across tasks and held-out spatial activation patterns. Spatial priors, when available, complement the text pathway by anchoring generation in regions of task space where language alone degrades, while retaining the compositional structure needed for counterfactual task specification. To our knowledge this is the first generative model of whole-cortex fMRI dynamics for unseen cognitive tasks, advancing counterfactual neuroscience and data-driven experimental design.

Functional Magnetic Resonance Imaging (fMRI) provides non-invasive access to dynamic brain activity by measuring blood oxygen level-dependent (BOLD) signals over time. However, the resource-intensive nature of fMRI acquisition limits the availability of high-fidelity samples required for data-driven brain analysis models. While modern generative models can synthesize fMRI data, they often remain challenging in replicating their inherent non-stationarity, intricate spatiotemporal dynamics, and physiological variations of raw BOLD signals. To address these challenges, we propose Dual-Spectral Flow Matching (DSFM), a novel fMRI generative framework that cascades dual frequency representation of BOLD signals with spectral flow matching. Specifically, our framework first converts BOLD signals into a wavelet decomposition map via a discrete wavelet transform (DWT) to capture globalized transient and multi-scale variations, and projects into the discrete cosine transform (DCT) space across brain regions and time to exploit localized energy compaction of low-frequency dominant BOLD coefficients. Subsequently, a spectral flow matching model is trained to generate class-conditioned cosine-frequency representation. The generated samples are reconstructed through inverse DCT and inverse DWT operations to recover physiologically plausible time-domain BOLD signals. This dual-transform approach imposes structured frequency priors and preserves key physiological brain dynamics. Ultimately, we demonstrate the efficacy of our approach through improved downstream fMRI-based brain network classification. The code is available at https://github.com/htew0001/DSFM.git .

Diagnosing Major Depressive Disorder (MDD) from functional magnetic resonance imaging (fMRI) using functional connectivity (FC) analysis requires large amounts of labeled data that are scarce in clinical settings. Existing augmentation methods synthesize FC matrices, which compress fMRI recordings into static pairwise summaries and discard temporal information. We propose fMRI-Diffusion, a framework that synthesizes region-of-interest (ROI)-level fMRI time series rather than FC matrices. A Temporal Transformer serves as the denoising network within a denoising diffusion probabilistic model, treating each time point as a token to capture temporal dependencies through self-attention. A supervised pretraining strategy initializes the Transformer with task-relevant representations before diffusion training, and FC matrices are derived from the synthesized time series for classification. Experiments on the REST-meta-MDD dataset show that augmenting training data with synthetic time series consistently improves diagnostic accuracy across ten classifiers, six parcellation atlases, and three acquisition sites. The method outperforms five recent FC-based synthesis approaches, with accuracy gains of up to 3.7 percentage points over the strongest baseline. Ablation studies confirm the contributions of both the Transformer-based denoiser and the pretraining strategy. Distributional fidelity metrics remain below 0.06 across all conditions, indicating close agreement between real and synthetic distributions. These findings suggest that synthesizing fMRI time series before FC computation preserves temporal information lost in matrix-level augmentation and provides a practical strategy for MDD diagnosis under limited data.